Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE*3-Leiden mice

Westerterp, M. (Marit)
Hoogt, C.C. (Caroline) van der
Haan, W. (Willeke) de
Offerman, E. (Erik)
Dallinga-Thie, G.M. (Geesje)
Jukema, J.W. (Jan Wouter)
Havekes, L.M. (Louis)
Rensen, P.C.N. (Patrick)

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Publication date

November 2006

DOI

10.1161/01.ATV.0000243925.65265.3c

Publisher

Ovid Technologies (Wolters Kluwer Health)

Abstract

OBJECTIVE - The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is still undergoing debate. Therefore, we evaluated the effect of human CETP expression on atherosclerosis in APOE*3-Leiden (E3L) mice with a humanized lipoprotein profile. METHODS AND RESULTS - E3L mice were crossbred with human CETP transgenic mice. On a chow diet, CETP expression increased plasma total cholesterol (TC) (+43%; P<0.05). To evaluate the effects of CETP on the development of atherosclerosis, mice were fed a Western-type diet containing 0.25% cholesterol, leading to 4.3-fold elevated TC levels in both E3L and CETP.E3L mice (P<0.01). On both diets, CETP expression shifted the distribution of cholesterol from high-density lip...